Long-term use of combo HRT: risks outweigh benefits; experts say that short-term therapy for menopausal symptoms is still viable. (Unopposed Estrogen Still Under Study).

WASHINGTON -- The use of combination hormone replacement therapy is expected to be largely limited to the short-term treatment of menopausal symptoms, now that a landmark trial has found that the overall risks of the therapy exceed its benefits.

The component of the Women's Health Initiative (WHI) comparing an estrogen-progestin combination with placebo showed a doubling in the risk of pulmonary emboli and deep vein thrombosis after an average of 5.2 years of use. There also were increased risks of stroke (41%), MI (29%), invasive breast cancer (26%), and total cardiovascular disease (22%).

The study the first randomized primary prevention trial of combination hormone replacement therapy (HRT), also found a 37% decrease in colorectal cancer risk and a 24% decrease in fracture risk in HRT users. Still, these benefits were not enough to offset the downside of treatment, prompting the sponsors of the federally funded study of 16,000 women to halt this part of the trial 3 years early

Dr. Jacques Rossouw, acting director of the WHI at the National Heart, Lung, and Blood Institute, stressed that the data pertain to the risk for an entire population, and that the average risk to an individual woman was small. For example, the risk of breast cancer per woman was on the order of less than 0.1% per year, "but if you apply that increased risk to an entire population and over several years, the number of women affected increases dramatically and becomes an important public health concern," he said at a press briefing announcing the halting of the WHI study.

Within days of the announcement of these findings, the Bala Cynwyd, Pa.-based law firm Schiffrin & Barroway announced a national class action lawsuit against Wyeth and Wyeth-Ayerst Research on behalf of users of Prempro, the HRT combination used in the study and marketed by Wyeth. The suit seeks the establishment of a medical monitoring fund for all women who have used Prempro, refunds for Prempro users, and compensation for "all victims for personal injuries and death."

Responding to the lawsuit, Natalie de Vane, director of public relations for Wyeth in Philadelphia, said in an interview, "We don't believe that there is any legal or factual basis for the claims."

Meanwhile, the balance of risks versus benefits for unopposed estrogen remains unclear in an ongoing WHI study that is scheduled to be completed in 3 years.